Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.531882
Title: Exploring the role of inflammatory mediators in the 1-methyl-4-phenly-1,2,3,6,-tetrahydropyridine (MPTP) mouse model of Parkinson's disease
Author: Martin, Heather Louise
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2010
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Abstract:
The roles of the potential immune regulators, peroxisome proliferator-activated receptors (PPARs) and the major histocompatibility complex class II (MHC II), were explored in the MPTP model of PD. Both PPARδ and PPARγ were expressed in the dopaminergic neurons affected in PD. PPARδ was also expressed in astrocytes whilst PPARγ was detected in microglia.  PPARδ appears to be important in cellular metabolic status as the PPARδ antagonist GSK0660 reduced cell viability without affecting cell death in SH-SY5Y cells, and PPARδ heterozygous mice showed functional compensation at the protein level.  To further support this the PPARδ agonist GW0742 was neuroprotective against MPTP toxicity in C57BL/6 mice.  PPARγ also has a role in neuronal survival as the antagonist GW9662 was toxic to neurons in vivo whilst the PPARγ agonist rosiglitazone showed neuroprotective effects in vitro reducing MPP+-induced reactive oxygen species formation, but these effects were PPARγ independent.  Rosiglitazone could not be used in vivo as it affected the bioactivation of MPTP.  MHC II was detected in astrocytes and a subset of microglial.  Genetic ablation of MHC II was neuroprotective against MPTP toxicity to the nigrostriatal dopaminergic neurons.  It also attenuated MPTP-induced reactive gliosis coincident with reductions in the levels of interferon-γ and tumour necrosis factor-α protein.  This thesis has demonstrated that activation of PPARδ and PPARγ and the ablation of MHC II provide neuroprotection in a model of PD, thus providing further support for manipulation of immune regulators as a potential therapeutic opportunity in PD.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.531882  DOI: Not available
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